Introduction:

Magnetic resonance imaging-guided transurethral ultrasound ablation (TULSA) of the prostate uses ultrasound to thermally coagulate tissue under real-time MRI guidance. Real-time feedback from closed-loop MRI thermometry automatically controls treatment parameters to match tissue response in the prescribed ablation volume. The pivotal study of TULSA (“TACT”, NCT02766543), which included a low- to intermediate-risk prostate cancer (PCa) population, has reached the end of the 5-year follow-up duration. Here we report the safety and efficacy outcomes at 5 years

Methods:

The TACT study enrolled 115 patients across 13 sites in 5 countries. Eligibility criteria included stage ≤ T2b, PSA ≤ 15 ng/mL, and Grade Group (GG) 1-2 disease. The protocol prescribed a single whole-gland TULSA treatment sparing the prostatic urethra and urinary sphincter, and repeat TULSA was not allowed.  The primary endpoints were PSA reduction and adverse events, both assessed at 1 year. Histologic control on 10-core biopsy, and prostate volume reduction on multiparametric MRI (mpMRI) were also assessed at 1 year. Other secondary endpoints, assessed to 5 years, included adverse events, quality of life, PSA, and the rate of salvage treatment.

Results:

Baseline (median [IQR]) age and PSA were 65 (59-69) years and 6.3 (4.6-7.9) ng/mL, with ≥GG2 disease in 72/115 men. At 1y, median prostate volume decreased from 37.3 to 2.8 cc (92%); 94/111 (85%) were free of ≥GG2 disease. By 5y, median (IQR) PSA decreased to 0.6 (0.18-1.9) ng/mL (n=68); 25 (21.7%) received salvage treatment (10 prostatectomy, 11 radiotherapy, 3 ADT, 1 surgery+radiation) without unexpected complications. Early predictors of treatment failure by 5 years included 1y PSA (OR=3; CI[1.7,5.4]) and visible lesion on 1y mpMRI (OR=12; CI[4.4,34]) (both p≤0.001). Failure modes include undertreatment due to patient selection or targeting error, and misalignment caused by intraprocedural swelling/motion. By 5 years, 61/66 (92%) recovered pad-free continence; 80/92 (87%) preserved erections sufficient for penetration. Grade 3 adverse events occurred in 12 men (10%), with no Grade≥4 event or rectal injury.

Conclusion:

Effective disease control is durable to 5 years after a single TULSA procedure, with a favorable safety profile. Favorable preservation of genitourinary quality of life is also durable to 5 years.  Treatment failure modes include screening and intraprocedural factors. While the pivotal study represents early experience with TULSA, the risk of failure is mitigated by modern protocols. Such protocols include best practices for screening for intraprostatic calcifications that can lead to undertreatment, refined strategies for device positioning, and thermal dose escalation to address undertreatment that is visible on intraprocedural imaging. Factors from intraprocedural imaging and early clinical follow-up can predict salvage therapy by 5 years.

Funding: Profound Medical Inc.